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Without adequate SAMe production from the methylation cycle, the brain cannot efficiently synthesize neurotransmitters like dopamine, serotonin, and norepinephrine, leading to mood disturbances, anxiety, and profound cognitive fatigue

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They send signals to the brain
In the duodenum, pancreatic enzymes break down haptocorrin which allows the pH change to trigger the transfer of B12 to the intrinsic factor (IF) which is a protein made by the stomach